Studies with certain isolated enzymes have demonstrated that various metabolites which are not themselves consumed or produced in the reaction are able to modify the activity of these key enzymes and that in such cases the enzyme velocity can be quantitatively related to the effector concentration by the Hill equation. While studies in many laboratories qualitatively supported the presumed importance of allosteric modulation of enzyme activity in the intact cell, these studies have not reproduced the quantitative relationships observed with purified enzymes. Our studies have been directed toward obtaining quantitative relationships between effector concentrations which occur in the cell and the concurrent activity of the affected enzyme. Initial studies have demonstrated that the steady state cellular levels of Fru-P2 and G-6-P in various conditions can be quantitatively related by the Hill equation to the cellular rates of glucose utilization and glycogen synthesis. These studies have provided the first quantitative evidence concerning the mechanism by which glycolysis, glucose utilization and glycogen synthesis are co-ordinately regulated in the intact cell. Alterations in the cellular level of ATP affect the velocity of PFK, the rate-limiting step of glycolysis, in a reciprocal manner. Alterations in this activity alter the cellular levels of G-6-P, a negative effector of glucose utilization and a positive effector of glycogen synthesis, and Fru-P2, a positive effector of both glucose utilization and glycogen synthesis. These co-ordinately linked changes provide for the coupling of ATP utilization and production in various metabolic circumstances. We propose to pursue the gathering of further evidence to further establish the validity of this mechanism and to elucidate other components involved in the coordinate regulation of energy metabolism by the intact cell. The intact E. coli cell serves as an elegant model study system.